Haemostatic parameters and vascular risk

Associations between increased plasma concentrations of the three haemostatic factors - fibrinogen, Factor VII and plasminogen activator inhibitor 1 (PAI-1) - and cardiovascular disease (CVD) have recently been demonstrated in epidemiological studies. The relative risk of CVD is increased by 2-3 times in subjects whose levels of fibrinogen fall within the upper third of the general distribution in comparison to those subjects who fall into the lower third; a positive correlation exists between increased Factor VII activity and cardiovascular mortality. Many studies have demonstrated that elevated levels of PAI-1 and tPA antigen are associated with CVD. Several studies have also shown that there are important associations between conventional risk factors for atherothrombosis and haemostatic factors. Fibrinogen levels are strongly linked with smoking, and Factor VII levels are linked with cholesterol, triglycerides and fat intake. PAI-1 and tPA antigen levels, on the other hand, are closely associated with insulin resistance. This paper discusses the principal genetic and environmental determinants of the plasma levels of each of these three haemostatic factors and relates them to the risk of developing CVD.